Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer

Part A: To assess the safety and tolerability and to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) of AZD0516 as monotherapy and in combination with anti-cancer agents.

Part B: To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.

To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.

The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result.

The PSA50 response rate is defined as the percentage of participants achieving ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result.

The PSA90 response rate is defined as the percentage of participants with a confirmed ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result.

The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA50 response (≥ 50% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.

The TTPSA response is defined as the time from the date of first dose of study intervention until the date of first documented PSA90 response (≥ 90% decrease in PSA from baseline, respectively) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.

The DoPSA50 is defined as the time from the date of first documented PSA50 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression.

The DoPSA90 is defined as the time from the date of first documented PSA90 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression.

The DRRPSA50 is defined as the percentage of participants who have a documented PSA50 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months.

The DRRPSA90 is defined as the percentage of participants who have a documented PSA90 response that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, with a duration of at least 6 months.

TTPSA progression is defined as time from the date of first dose of study intervention until the date of documented PSA progression or the last PSA result in the absence of progression.

The percentage change from baseline in PSA levels will be assessed.

The ORR is defined as the percentage of participants with a confirmed tumour response of Complete Response (CR) or Partial Response (PR).

The BOR is defined as the best overall visit response achieved by participant.

The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until the date of radiographic disease progression or censoring.

The DRR is defined as the percentage of participants who have a confirmed response with a duration of at least 6 months.

The DCR is defined as the percentage of participants who have a BOR of confirmed CR or PR or Stable Disease (SD).

The TTR is defined as the time from the date of first dose of study intervention until the date of first documented objective response, which is subsequently confirmed.

The best percentage change from baseline in tumour size is the largest decrease (or smallest increase) from baseline for a participant, using response evaluation criteria in solid tumors (RECIST) v1.1 assessments.

rPFS is defined as the time from date of first dose of study intervention until the date of objective disease progression according to RECIST v1.1 (for soft tissue disease) and prostate cancer working group 3 (PCWG3) criteria (for bone disease) as assessed by the investigator at the local site, or death (by any cause in the absence of progression).

OS is defined as the time from date of first dose of study intervention until death due to any cause.

To characterise the pharmacokinetics (PK) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

To characterise the PK (AUC) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

To characterise the PK (Cmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

To characterise the PK (tmax) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

To characterise the PK (CL) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

To characterise the PK (t1/2) of AZD0516 when given as monotherapy and in combination with anti-cancer agents.

This refers to the total amount of antibody present in a sample, regardless of whether it's attached to a drug (conjugated) or not (unconjugated). It includes a) Antibodies that are linked to the drug(conjugated antibodies) b) Antibodies that are not linked to any drug (unconjugated antibodies). This measurement gives an overall picture of the antibody concentration, which is important for understanding the pharmacokinetics of the ADC.

The "payload" typically refers to the cytotoxic drug that is attached to the antibody in an antibody drug conjugate (ADC).

"Unconjugated payload" means the drug molecules that are not attached to any antibody.

"Total unconjugated payload" refers to the total amount of free drug present in the sample.

This measurement is crucial for assessing the stability of the ADC and understanding how much of the drug has been released from the antibody.

Target expression of STEAP2 will be evaluated using an analytically validated IHC assay.

Expression of STEAP2 will be evaluated using an analytically validated IHC assay.

To determine the immunogenicity of AZD0516 as monotherapy and in combination with anti-cancer agents.

To further assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents.